Prezista 600 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

PREZISTA 600 mg film-coated tablets

darunavir

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

1. What PREZISTA is and what it is used for
2. What you need to know before taking PREZISTA
3. How to take PREZISTA
4. Possible side effects
5. How to store PREZISTA
6. Contents of the pack and other information

1. What PREZISTA is and what it is used for

What is PREZISTA?

PREZISTA contains the active substance darunavir. PREZISTA is an antiretroviral medicine used to treat Human Immunodeficiency Virus (HIV) infection. It belongs to a group of medicines called protease inhibitors. PREZISTA reduces the amount of HIV in your body. As a result, your immune system will improve and the risk of developing HIV-related illnesses will decrease.

What is it used for?

PREZISTA is used to treat adults and children from 3 years of age who weigh at least 15 kilograms and who have previously used other antiretroviral medicines.

PREZISTA must be taken together with a low dose of ritonavir and other HIV medicines. Your doctor will advise you on the most appropriate combination of medicines for you.

2. What you need to know before starting to take PREZISTA

Do not take PREZISTA

• if you are allergic to darunavir or to any of the other ingredients of this medicine (listed in section 6) or to ritonavir.
• if you have severe liver problems. Ask your doctor if you are unsure about the severity of your liver disease. Additional tests may be required.

Do not combine PREZISTA with any of the following medicines

If you are taking any of these drugs, consult your doctor to switch to another medicine.

Do not combine PREZISTA with products containing St. John’s wort (Hypericum perforatum).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to take PREZISTA.

PREZISTA does not cure HIV infection. While taking this medicine, you may still transmit HIV to others, although effective antiviral treatment reduces this risk. Consult your doctor about the necessary precautions to avoid infecting others.

People taking PREZISTA may develop other infections or diseases associated with HIV infection. You should maintain regular contact with your doctor.

People taking PREZISTA may develop a skin rash. It is uncommon for the rash to be severe or potentially life-threatening. Please consult your doctor if you develop a rash.

Patients taking PREZISTA and raltegravir (for HIV infection) may experience rashes (usually mild or moderate) more frequently than patients taking either of these medicines separately.

Inform your doctor about your condition BEFORE and DURING treatment

Make sure you check the following points and inform your doctor if any apply to you.

• Inform your doctor if you have had any liver disease, including hepatitis B or C infection. Your doctor will assess the severity of your liver disease before deciding whether you can take PREZISTA.

• Inform your doctor if you have diabetes. PREZISTA may cause an increase in blood sugar levels.

• Inform your doctor immediately if you notice any signs of infection (e.g., swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infections, signs and symptoms of inflammation due to previous infections may occur shortly after starting HIV treatment.

These symptoms are believed to result from an improved immune response, enabling the body to fight infections that were previously present without apparent symptoms.

• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after you have started taking medicines for your HIV infection. Autoimmune disorders may appear many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving upward toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Inform your doctor if you have haemophilia. PREZISTA may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (e.g., used to treat certain infections).
• Inform your doctor if you notice any bone or muscle problems. Some patients using combination antiretroviral therapy may develop a bone disorder called osteonecrosis (bone tissue death caused by reduced blood supply to the bone). Among the many risk factors for this condition are duration of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, and higher body mass index. Signs of osteonecrosis include joint pain, discomfort, and stiffness (especially in the hips, knees, and shoulders) and difficulty moving. If you notice any of these symptoms, please consult your doctor.

Elderly population

PREZISTA has only been used in a limited number of patients aged 65 years or older. If you belong to this age group, please discuss with your doctor whether you can use PREZISTA.

Children

PREZISTA is not used in children under 3 years of age or weighing less than 15 kilograms.

Taking PREZISTA with other medicines

Inform your doctor or pharmacist if you are taking or have recently taken any other medicines.

Some medicines must not be combined with PREZISTA. The list can be found in the section “Do not combine PREZISTA with any of the following medicines:”

In most cases, PREZISTA can be combined with HIV medicines belonging to other classes [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. PREZISTA co-administered with ritonavir has not been studied with all protease inhibitors (PIs) and must not be used with other HIV protease inhibitors. In some cases, the dose of other medicines may need to be adjusted. Therefore, if you are taking other anti-HIV medicines, always inform your doctor and follow their instructions carefully regarding which medicines can be combined.

The following products may reduce the effectiveness of PREZISTA. Inform your doctor if you are taking:

• Phenobarbital, phenytoin (to prevent seizures)
• Dexamethasone (a corticosteroid)
• Efavirenz (for HIV infection)
• Boceprevir (to treat hepatitis C infection)
• Rifapentine, rifabutin (medicines to treat certain infections such as tuberculosis)
• Saquinavir (for HIV infection).

PREZISTA may also affect the effects of other medicines. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disorders), as the therapeutic or adverse effects of these medicines may be increased.
• Apixaban, edoxaban, rivaroxaban, warfarin (to reduce blood clotting), as the therapeutic or adverse effects of these medicines may be altered; your doctor may perform blood tests.
• Hormonal contraceptives based on oestrogens and hormone replacement therapies. PREZISTA may reduce their effectiveness. For birth control, non-hormonal alternative contraceptive methods are recommended.
• Ethinylestradiol/drospirenone. PREZISTA may increase the risk of elevated potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to reduce blood cholesterol). There may be an increased risk of muscle damage. Your doctor will determine the most suitable cholesterol-lowering treatment based on your individual circumstances.
• Clarithromycin (antibiotic)
• Cyclosporine, everolimus, tacrolimus, sirolimus (to suppress the immune system), as the therapeutic or adverse effects of these medicines may be increased. Your doctor may perform additional tests.
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory eye, joint, and muscle conditions, and other inflammatory disorders. If alternatives cannot be used, their use should only occur after clinical evaluation and with close monitoring by your doctor for corticosteroid-related adverse effects.
• Buprenorphine/naloxone (medicines for opioid dependence treatment)
• Salmeterol (medicine for asthma treatment)
• Artemether/lumefantrine (a combination of medicines for treating malaria)
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (for cancer treatment)
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder called pulmonary arterial hypertension)
• Glecaprevir/pibrentasvir, simeprevir (to treat hepatitis C infection)
• Fentanyl, oxycodone, tramadol (for pain treatment)
• Fesoterodine, solifenacin (for treating urological disorders).

In certain cases, the dose of some medicines may need to be adjusted, as their therapeutic or adverse effects, or those of PREZISTA, may be affected when combined.

Inform your doctor if you are taking:

• Alfentanil (a short-acting injectable strong painkiller used during surgical procedures)
• Digoxin (for treating certain heart disorders)
• Clarithromycin (antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be administered after medical evaluation.
• Rifabutin (for bacterial infections)
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary circulation)
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (for treating depression and anxiety)
• Maraviroc (for treating HIV infection)
• Methadone (for treating narcotic dependence)
• Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain)
• Colchicine (for treating gout or familial Mediterranean fever)
• Bosentan (for treating high blood pressure in the pulmonary circulation)
• Buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam when administered by injection, zolpidem (sedative agents)
• Perphenazine, risperidone, thioridazine (for treating psychiatric conditions).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.

Taking PREZISTA with food and drinks

See section 3 “How to take PREZISTA.”

Pregnancy and breastfeeding

Inform your doctor immediately if you are pregnant, planning to become pregnant, or breastfeeding. Pregnant or breastfeeding women should not take PREZISTA with ritonavir unless specifically instructed by their doctor. Pregnant or breastfeeding women should not take PREZISTA with cobicistat.

It is recommended that HIV-infected women do not breastfeed their babies, as there is a risk that the babies could become infected with HIV through breast milk, as well as due to unknown effects of the medicine on infants.

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

Do not operate tools or machinery or drive if you experience dizziness after taking PREZISTA.

PREZISTA tablets contain sunset yellow FCF (E110), which may cause allergic-type reactions.

3. How to take PREZISTA

Follow exactly the dosing instructions provided in this leaflet or as prescribed by your doctor, pharmacist, or nurse. If in doubt, consult your doctor, pharmacist, or nurse.

Do not stop taking PREZISTA or ritonavir without first consulting your doctor, even if you feel better.

Once treatment has been started, do not change the dose or dosing schedule or interrupt treatment without consulting your doctor.

Dosage for adults who have not previously taken antiretroviral medicines (to be determined by your doctor)

You will require a different dose of PREZISTA that cannot be administered with these 600-milligram tablets. Other PREZISTA strengths are available.

Dosage for adults who have previously taken antiretroviral medicines (to be determined by your doctor)

The dose is:

• 600 milligrams of PREZISTA (2 tablets containing 300 milligrams of PREZISTA or 1 tablet containing 600 milligrams of PREZISTA) together with 100 milligrams of ritonavir twice daily.

Or

• 800 milligrams of PREZISTA (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) together with 100 milligrams of ritonavir once daily. The 400-milligram and 800-milligram PREZISTA tablets are only used for the 800-milligram once-daily regimen.

Please consult your doctor to determine which dose is right for you.

Instructions for adults

• Always take PREZISTA with ritonavir. PREZISTA does not work properly without ritonavir.
• In the morning, take one 600-milligram PREZISTA tablet together with 100 milligrams of ritonavir.
• In the evening, take one 600-milligram PREZISTA tablet together with 100 milligrams of ritonavir.
• Take PREZISTA with food. PREZISTA does not work properly without food. The type of food is not important.
• Swallow the tablets with a drink, which may be water or milk.

The 75-milligram and 150-milligram PREZISTA tablets and the 100-milligram per milliliter oral suspension have been developed for use in children, but in some cases may also be used in adults.

Dosage for children aged 3 years and older weighing at least 15 kilograms who have not previously taken antiretroviral medicines (to be determined by your child's doctor)

The doctor will calculate the correct daily dose based on the child's weight (see table below). This dose must not exceed the recommended adult dose of 800 milligrams of PREZISTA together with 100 milligrams of ritonavir once daily.

The doctor will inform you of the number of PREZISTA tablets and the amount of ritonavir (capsules, tablets, or solution) your child should take.

Dosage for children aged 3 years and older weighing at least 15 kilograms who have previously taken antiretroviral medicines (to be determined by your child's doctor)

The doctor will determine the correct dose based on the child's weight (see table below). The doctor will decide whether a once-daily or twice-daily dosing schedule is appropriate for the child. This dose must not exceed the recommended adult dose, which is either 600 milligrams of PREZISTA with 100 milligrams of ritonavir twice daily or 800 milligrams of PREZISTA with 100 milligrams of ritonavir once daily. The doctor will inform you of the number of PREZISTA tablets and the amount of ritonavir (capsules, tablets, or solution) your child should take. Additional PREZISTA strengths are available to achieve the appropriate dosing regimen.

The PREZISTA oral suspension is also available. Your doctor will advise whether PREZISTA tablets or oral suspension are suitable for your child.

Twice-daily dosing

• The doctor may consider the 800-milligram once-daily dose for children aged 12 years or older who weigh at least 40 kilograms. This dose cannot be administered with 600-milligram tablets. Other PREZISTA formulations are available.

Ritonavir oral solution: 80 milligrams per milliliter

Instructions for children

• The child must always take PREZISTA with ritonavir. PREZISTA cannot work properly without ritonavir.
• The child must take the prescribed dose of PREZISTA and ritonavir either twice daily or once daily. If PREZISTA is prescribed twice daily, the child should take one dose in the morning and one in the evening. Your child's doctor will determine the appropriate dosing schedule.
• The child must take PREZISTA with food. PREZISTA cannot work properly without food. The type of food is not important.
• The child must swallow the tablets with a drink such as water or milk.
• The 75-milligram and 150-milligram PREZISTA tablets and the 100-milligram per milliliter oral suspension have been developed for use in children weighing less than 40 kilograms, but in some cases may also be used in adults.

Removing the child-resistant cap

If you take more PREZISTA than you should

Inform your doctor, pharmacist, or nurse immediately.

If you forget to take PREZISTA

If you remember within 6 hours , take the missed dose immediately. Always take it with ritonavir and food. If you remember after 6 hours , skip that dose and take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

Do not stop taking PREZISTA without first talking to your doctor

HIV medicines can help you feel better. Even if you feel well, do not stop taking PREZISTA. Talk to your doctor first.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

During HIV treatment, there may be an increase in weight and in blood glucose and lipid levels. This may be partly related to the recovery of health and lifestyle, and in the case of blood lipids, sometimes to HIV medicines themselves. Your doctor will monitor these changes.

Like all medicines, this medicine can cause adverse effects, although not everybody gets them.

Tell your doctor if you develop any of the following adverse effects.

Cases of liver problems, which occasionally may be serious, have been reported. Your doctor will perform a blood test before you start treatment with PREZISTA. If you have a chronic infection caused by hepatitis B or C, your doctor will check your blood tests more frequently, as there is a higher risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin and whites of the eyes, darkening (tea-colored) of the urine, pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side below your ribs.

Skin rash (more frequent when used in combination with raltegravir), itching. Skin rash is usually mild to moderate. A skin rash may also be a symptom of a rare but serious condition. Therefore, it is important to talk to your doctor if you develop a rash. Your doctor will advise you on how to manage symptoms or whether to discontinue PREZISTA.

Other serious adverse effects included diabetes (frequent) and inflammation of the pancreas (uncommon).

Very common adverse effects (may affect more than 1 in 10 people)

• Diarrhea

Common adverse effects (may affect up to 1 in 10 people)

• Vomiting, nausea, abdominal pain or distension, upper abdominal pain (dyspepsia)
• Flatulence
• Headache, fatigue, dizziness, somnolence, numbness sensation
• Numbness, tingling, or pain in the hands or feet, loss of strength, difficulty falling asleep

Uncommon adverse effects (may affect up to 1 in 100 people)

• Chest pain, changes in electrocardiogram, rapid heartbeat
• Decreased or abnormal skin sensitivity, tingling, attention disorder, memory loss, difficulty maintaining balance
• Breathing difficulty, cough, nosebleed, throat irritation
• Inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort
• Constipation, belching
• Kidney failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night
• Hives, severe swelling of the skin and other tissues (especially lips or eyes), eczema
• Excessive sweating, night sweats, alopecia, acne, scaly skin, nail discoloration
• Muscle pain, muscle cramps or weakness, limb pain, osteoporosis
• Reduced thyroid gland function. This can be seen in a blood test.
• Hypertension (increased blood pressure), flushing
• Red or dry eyes
• Fever, swelling of the lower limbs due to fluid retention, malaise
• Irritability, pain
• Symptoms of infection, herpes simplex
• Erectile dysfunction, breast enlargement
• Difficulty falling asleep, somnolence, depression, anxiety, abnormal dreams
• Decreased sex drive

Rare adverse effects (may affect up to 1 in 1,000 people)

• A reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, facial swelling or swollen lymph nodes, increased eosinophils (a type of white blood cell), liver, kidney, or lung damage]
• Myocardial infarction, slow heartbeat, palpitations
• Visual disturbance
• Chills, unusual sensation
• A feeling of confusion or disorientation, altered mood, agitation
• Fainting, epileptic seizure, changes or loss of taste
• Mouth ulcers, vomiting blood, lip inflammation, dry lips, coated tongue
• Nasal discharge
• Skin lesions, dry skin
• Muscle or joint stiffness, joint pain with or without inflammation
• Changes in certain blood cell or biochemical values. These changes can be seen in blood and/or urine tests. Your doctor will explain them to you. For example: increase in certain white blood cells.

Some adverse effects are typical of HIV medicines belonging to the same class as PREZISTA. These are:

• Muscle pain, tenderness, or weakness. In rare cases, these muscle disorders may be serious.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of PREZISTA

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and on the bottle, after EXP. The expiry date refers to the last day of the month indicated.

PREZISTA does not require any special storage conditions.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of PREZISTA

• The active substance is darunavir. Each tablet contains 600 milligrams of darunavir (as ethanolate).
• • The other components are microcrystalline cellulose, anhydrous colloidal silica, crospovidone and magnesium stearate. The coating contains poly(vinyl alcohol) – partially hydrolysed, macrogol 3350, titanium dioxide (E171), talc and sunset yellow FCF (E110).
• • This medicine contains less than 1 mmol of sodium (23 mg) per dose unit; this is essentially “sodium-free”.

Nature and contents of the container

Film-coated tablet, oval-shaped, orange in colour, marked with TMC on one side and
600MG on the other side.

60 tablets in a plastic bottle.

PREZISTA is also available as film-coated tablets of 75 mg, 150 mg, 300 mg, 400 mg, 800 mg and as oral suspension of 100 mg per millilitre.

Marketing Authorisation Holder

Janssen-Cilag International NV, Turnhoutseweg 30, 2340 Beerse, Belgium

Manufacturer

Janssen-Cilag SpA, Via C. Janssen, Borgo San Michele, 04100 Latina, Italy

For more information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet: {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.